Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2

Shin, Young Sup; Lee, Jun Young; Noh, Soojin; Kwak, Yoonna; Jeon, Sangeun; Kwon, Sunoh; Jin, Young‐Hee; Jang, Min Seong; Kim, Seungtaek; Song, Jungsuk; Kim, Hyoung Rae; Park, Chul Min

doi:10.1016/j.bmcl.2020.127667

Cited by 24 publications

(21 citation statements)

References 11 publications

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“…However, Compounds 4c exhibited the highest antiviral activity in vitro with IC50 was 758.8108 mM. Our results were in accordance with Shin et al [ 37 ] who proved that cyclic sulfonamide derivatives will be the savior against SARS-CoV-2 because of their IC50 inhibition reached 0.88 μM with no proved cytotoxic effect (CC50 > 25 μM), and high oral bioavailability equaled 77% with good metabolic stability. He et al [ 38 ] tested the antiviral activity of some purine nucleoside derivatives containing a sulfonamide moiety and it was proved that the antiviral activity was related to the immune induction effect.…”

Section: Resultssupporting

confidence: 90%

Anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids using in silico and in vitro analyses

Shaaban

Elwakil

Hamed

et al. 2021

Chemometrics and Intelligent Laboratory Systems

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic fatal infection with no known treatment. The severity of the disease and the fast viral mutations forced the scientific community to search for potential solution. Here in the present manuscript, some benzofused1,2,3triazolesulfonamide hybrids were synthesized and evaluated for their anti- SARS-CoV-2 activity using in silico prediction then the most potent compounds were assessed using in-Vitro analysis. The in-Silico study was assessed against RNA dependent RNA polymerase, Spike protein S1, Main protease (3CLpro) and 2'-O-methyltransferase (nsp16). It was found that 4b and 4c showed high binding scores against RNA dependent RNA polymerase reached -8.40 and -8.75 Kcal/mol, respectively compared to the approved antiviral (remdesivir -6.77 Kcal/mol). Upon testing the binding score with SARS-CoV-2 Spike protein it was revealed that 4c exhibited the highest score (-7.22 Kcal/mol) compared to the reference antibacterial drug Ceftazidime (-6.36 Kcal/mol). Surprisingly, the two compounds 4b and 4c showed the highest binding scores against SARS-CoV-2 3CLpro (-8.75, -8.48 Kcal/mol, respectively) and nsp16 (- 8.84 and – 8.89 Kcal/mol, respectively) displaying many types of interaction with all the enzymes binding sites. The derivatives 4b and 4c were examined in vitro for their potential anti-SARS-CoV-2 and it was revealed that 4c was the most promising compound with IC50 reached 758.8108 mM and complete (100%) inhibition of the binding of SARS-CoV-2 virus to human ACE2 can be accomplished by using 0.01 mg.

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Section: Resultssupporting

confidence: 90%

Anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids using in silico and in vitro analyses

Shaaban

Elwakil

Hamed

et al. 2021

Chemometrics and Intelligent Laboratory Systems

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“… Gao et al, 2020 ). Of note, it has recently been reported that cyclic sulfonamide derivatives are potent inhibitors (IC 50 = 0.9-3.1 μM) of SARS-CoV-2 in Vero cells (Y. S. Shin et al, 2020 ).…”

Section: Antidiabetic Drugs and Ace2mentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

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The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

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“…The derivatives 12a and 12d were found to be roughly three-fold more effective as inhibitors of α-glucosidase enzymes compared to acarbose. The increase in bioactivity with the introduction of EWGs in the benzoyl and N-phenyl moieties was also witnessed during the evaluation of previously reported 1,2-benzothiazine-N-arylacetamides as SARS-CoV-2 inhibitors [51]. In the series 12a-m, the variation in the position of nitro, chloro, and bromo substituents failed to enhance the enzymatic inhibition potential of the compounds.…”

Section: α-Glucosidase Inhibition (In Vitro Analysis)mentioning

confidence: 78%

“…The derivative 3 (Figure 1) showed the most promising activity with an IC 50 value of 0.041 µM [49]. Recently, Shin and coworkers reported novel 1,2-benzothiazine-N-arylacetamides as SARS-CoV-2 inhibitors and among them compound 4 (Figure 1) showed robust activity with an IC 50 value of 0.88 µM [51]. Furthermore, 2-(2-(4-bromo-2fluorobenzyl)-1,1-dioxido-2H-benzo[e][1,2]thiazin-4(3H)-ylidene)acetic acid was proved to be a good aldose-reductase inhibitor with an IC 50 value of 0.11 µM [39].…”

Section: Biological Activitymentioning

confidence: 99%

Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach

et al. 2021

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Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.

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Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2

Abstract: Graphical abstract

Cited by 24 publications

References 11 publications

Anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids using in silico and in vitro analyses

Anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids using in silico and in vitro analyses

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach

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